US2773900A - Substituted aryl amino alkyl ethers - Google Patents
Substituted aryl amino alkyl ethers Download PDFInfo
- Publication number
- US2773900A US2773900A US467635A US46763554A US2773900A US 2773900 A US2773900 A US 2773900A US 467635 A US467635 A US 467635A US 46763554 A US46763554 A US 46763554A US 2773900 A US2773900 A US 2773900A
- Authority
- US
- United States
- Prior art keywords
- ether
- acid
- phenylphenyl
- substituted aryl
- alkyl ethers
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH] (Somatotropin)
Definitions
- the compounds of this invention are pharmaceutically useful as drug-prolonging agents, for example, in prolonging and potentiating the action of barbiturates and analgesics.
- the above novel compounds can be incorporated into tablets, capsules, suspensions, emulsions, solutions, and other like pharmaceutical forms, using the appropriate pharmaceutical extending media as known to the art.
- the compounds exhibit their usefulness as drug-prolonging agents when administered orally or parenterally in conjunction with the drug whose action is to be prolonged.
- R1 and Re can be the same or different lower alkyl radicals such as methyl, ethyl, propyl, isopropyl, and the like.
- acids which can form nontoxic, pharmaceutically useful acid addition salts with the bases of the above formula are the following: hydrochloric acid, hydrobromic acid, sulfuric acid, ascorbic acid, phosphoric acid, tartaric acid, maleic acid, succinic acid, oxalic acid, and the like.
- novel amino alkyl phenyl ethers provided by my invention are prepared as follows: An alkali metal salt of the substituted phenol is prepared in a suitable solvent. To this stirred mixture is added a dialkyl-fi-haloethyl amine in the form of its free base. The reaction mixture is heated for several hours, and is then filtered to remove inorganic salts. The resulting amino alkyl phenyl ether is contained in the filtrate and is isolated and purified by conventional means, such including extraction into dilute acid, neutralization of the acid extract, extraction back into an organic phase, distillation of the free base, and preparation therefrom of a crystalline acid addition salt.
- I'hel-eoma bined, acid. extracts were made ba sie' and theibaseiiusoluble material, comprising 2,4;diehloro6-ghenylphenyl; di-i ethyl-a'minoethyl ether was extracted into .diethyl ether.
- a base represented by the following formula 3 A base represented by the fol1owing,formula References Cited in the file ofl this patent I UNITED 'STATESPATENTS 2,187,723 2,217,660 Alquist et a1. Oct. 15, 1940 Binkleyet a1.” Mar.- 1' 1955 Alquist et a1. Jan. 23, 1940
Description
United States Patent SUBSTITUTED ARYL AlVflNO ALKY L ETHERS Jack Mills, Glenns Valley, Ind., assignor to Eli Lilly and Company, Indianapolis, 11111., a corporation of Indiana No Drawing. Application November 8, 1954, Serial No. 467,635
4 Claims. (Cl. 260570.7)
m-Q-o-om-cm-r/ I Rs 01 in which R1 and R2 represent lower alkyl groups and R3 is a hydrogen or a chlorine atom. The compounds of this invention are pharmaceutically useful as drug-prolonging agents, for example, in prolonging and potentiating the action of barbiturates and analgesics. For such purposes the above novel compounds can be incorporated into tablets, capsules, suspensions, emulsions, solutions, and other like pharmaceutical forms, using the appropriate pharmaceutical extending media as known to the art. The compounds exhibit their usefulness as drug-prolonging agents when administered orally or parenterally in conjunction with the drug whose action is to be prolonged.
In the above formula, R1 and Re can be the same or different lower alkyl radicals such as methyl, ethyl, propyl, isopropyl, and the like. Among the acids which can form nontoxic, pharmaceutically useful acid addition salts with the bases of the above formula are the following: hydrochloric acid, hydrobromic acid, sulfuric acid, ascorbic acid, phosphoric acid, tartaric acid, maleic acid, succinic acid, oxalic acid, and the like.
Broadly, the novel amino alkyl phenyl ethers provided by my invention are prepared as follows: An alkali metal salt of the substituted phenol is prepared in a suitable solvent. To this stirred mixture is added a dialkyl-fi-haloethyl amine in the form of its free base. The reaction mixture is heated for several hours, and is then filtered to remove inorganic salts. The resulting amino alkyl phenyl ether is contained in the filtrate and is isolated and purified by conventional means, such including extraction into dilute acid, neutralization of the acid extract, extraction back into an organic phase, distillation of the free base, and preparation therefrom of a crystalline acid addition salt.
My invention is further illustrated by the following specific examples:
EXAMPLE 1 Preparation of 2-chloro-6-phenylphenyl dimethylaminoethyl ether hydrochloride 2.5 g. of sodium metal were reacted with 200 m1. of ethanol to form a solution of sodium ethoxide. 20.5 g. of 2-chloro-6-phenylphenol were added with stirring to 2,773,900 vPatented Dec. 11, 1956 this solution, yielding the sodium salt of the phenol. 18
- g. of dimethyl-p-chloroethylamine were next added to the reaction mixture. After addition of the amine was complete, the reaction mixture was heated to refluxing temperature for about 12 hours, thus forming 2-chloro-6- phenylphenyl dimethylaminoethy-l ether. The reaction mixture was cooled and was filtered to remove inorganic salts. the alcohol. The organic layer which separated was shaken with dilute hydrochloric acid, the 2-chloro-6-phenylphenyl dimethylaminoethyl ether being extracted into theaqueous acid layer as the soluble hydrochloride salt.
ether solutions of the said base, there were obtained the corresponding maleate and phosphate salts, respectively. Likewise, other salts such as the tartrate, ascorbate and The acid extract was then made basic with aqueous sodium hydroxide solution and the amino-ether which separated'from solution was extracted into diethyl ether. The
ether layer was washed with water, was dried with anhydrous magnesium sulfate, and the ether was evaporated off. The oily residue comprising 2chl0r06-phenylphenyl dimethylaminoethyl etherwas distilled. The distillate was dissolved in ether and HCl gas bubbled into the solution in order to prepare the hydrochloride salt of 2-chloro- 6-phenylphenyl diinethylaminoethyl ether. After recrys tallization, this hydrochloride salt melted at about.
Other salts of 2-chloro-6-phenylphenyl dimethylaminoethyl ether are made by dissolving the free base in ether and adding an equivalent weight of the desired acid thereto. Thus, by addition of maleic or phosphoric acid to Preparation of 2,4-dich[moo-phenylphenyl dimezhylaminoethyl ether A toluene solution containing 23.9 g. of 2,4-dichloro- 6-phenylphenol was added to a refluxing toluene suspension of 5.2 g. of sodium hydride, thus forming the sodium salt of the phenol. Rcfluxing was continued for one hour after addition of the phenol was complete. An ether solution containing 21.6 g. of dimethyl-fl-chloroethylamine was then added dropwise to the reaction mixture, and heating at refluxing temperature was continued overnight. By this reaction 2,4-dichloro-6-phenylphen yl dimethylaminoethyl ether was formed. The reaction mixture was poured over ice and 500 ml. of diethyl ether were added thereto. The organic layer was separated and then extracted twice with 200 ml. portions of 10 percent hydrochloric acid, the amino-ether being extracted into the acidic layer at this point. The acidic extracts were combined, were made basic with aqueous sodium hydroxide, were extracted with two 500 ml. portions of ether, and the amino-ether extracted back into diethyl ether. The combined ether extracts, which now contained the free base of 2,4-dichloro-6-phenylphenyl dimethylaminoethyl ether were dried and filtered, and the filtrate was distilled. 2,4-dichloro-6-phenylphenyl dimethylaminoethyl ether distilled at about 138-l56 C. at a pressure of about 0.4 mm. of mercury. The yield was 22 g.
The hydrochloride salt of 2,4-dichloro-6-phenylphenyl dimethylaminoethyl ether was prepared and purified by the procedures disclosed in Example 1. It melted at about 186-187 C. Analysis showed the presence of,
About 1 1. of diethyl ether was added to dilute EXAMPLE 3 n r Preparation of 2,4'dichl0ro-6-phenylphenyl diethylaminoethyl ether A solution of sodiumethoxide was; preparedibjt, dis
solving 2.5 g. of sodium in 200 ml. of ethanol; 26, 3 g.. of 2,4-dichloro-6-phenylphenol were added dropwise 0-- this solution, thus formingv the sodium saltpof theghenoL. To the resulting solution'were added 23. g. of diethyl-B chloroethylamine and the mixture was heated at refluxing temperature overnight. The reaction mixture containing the desired 2,4-dichloro-6-phenylphenyl diethyglaminq. ethyl ether was poured, over. ice, andthe aminQ-etherwas extractedinto diethyl ether. The etherelayer -wasithenextracted. twice with dilute. hydrochloric, acid. I'hel-eoma bined, acid. extracts were made ba sie' and theibaseiiusoluble material, comprising 2,4;diehloro6-ghenylphenyl; di-i ethyl-a'minoethyl ether was extracted into .diethyl ether.
The, ether layer was washediwith Water, was. dried; over anhydrous magnesium sulfate, and was .filtered: to-remoye.
th'edrying agent, Ttie solventwasl euagoratedintvacuo, .andithe residue of 2-, 4.-di'chloro.-6+phenylphenyl diethylar'ninoethyl ether wassdistille'd- The fraction. boiling betweeuabout 150-162" C. at a pressureof about; 1,0
of, mercury was collected. measure waseonyerted to the. hydrobroinide salt by t hernethqd 0f; Exan igleel. The resulting crystallinematerial, 2-, 4dichloro-6-phenylphenyl diethylaminoethyl' ether hydrolf romide melted at, about 131132 C. Analysis shbw ed'the rpresence of.
18.82 percent bromine as comparedwitl1 thi6aleulated value of 19.08. percent.- r
I claim; v
1; A pharm acologically active comfloundof theclasst consisting of a base and itsfnontoxie pharmaceutically usefullacid addition salts", said base beingrepresented by I the formula in which R1 and R2 represent lower alkyl groups and Rs i'scliosen from" the clas'scon'si'sting 'of' a'hyd'r'oge'n atom" and a chlorine atom.
2. A base represented by the following formula 3. A base represented by the fol1owing,formula References Cited in the file ofl this patent I UNITED 'STATESPATENTS 2,187,723 2,217,660 Alquist et a1. Oct. 15, 1940 Binkleyet a1." Mar.- 1' 1955 Alquist et a1. Jan. 23, 1940
Claims (1)
1. A PHARMACOLOGICALLY ACTIVE COMPOUND OF THE CLASS CONSISTING OF A BASE AND ITS NONTOXIC PHARMACEUTICALLY USEFUL ACID ADDITION SALTS, SAID BASE BEING REPRESENTED BY THE FORMULA
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US467635A US2773900A (en) | 1954-11-08 | 1954-11-08 | Substituted aryl amino alkyl ethers |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US467635A US2773900A (en) | 1954-11-08 | 1954-11-08 | Substituted aryl amino alkyl ethers |
Publications (1)
Publication Number | Publication Date |
---|---|
US2773900A true US2773900A (en) | 1956-12-11 |
Family
ID=23856490
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US467635A Expired - Lifetime US2773900A (en) | 1954-11-08 | 1954-11-08 | Substituted aryl amino alkyl ethers |
Country Status (1)
Country | Link |
---|---|
US (1) | US2773900A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2879293A (en) * | 1957-02-19 | 1959-03-24 | Hoffmann La Roche | Benzylamine derivatives |
US3139430A (en) * | 1960-12-20 | 1964-06-30 | Merck & Co Inc | 2-dialkylaminoalkoxy-6-substituted naphthalenes useful as new anticholesteremic agents |
US3178420A (en) * | 1959-06-25 | 1965-04-13 | Richardson Merrell Inc | Amino-2-hydroxy-1-propoxy benzal derivatives of fluorene and xanthene |
US3213140A (en) * | 1960-09-06 | 1965-10-19 | Lilly Co Eli | 2-phenyl-4, 6-dichlorophenoxyethylamine and salts thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2170324A (en) * | 1937-09-15 | 1939-08-22 | Hanna Samuel Orr | Dust evacuating device |
US2187723A (en) * | 1938-07-27 | 1940-01-23 | Dow Chemical Co | Primary xenoxy-alkyl amines |
US2217660A (en) * | 1938-07-27 | 1940-10-15 | Dow Chemical Co | Secondary xenoxy-alkyl amines |
-
1954
- 1954-11-08 US US467635A patent/US2773900A/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2170324A (en) * | 1937-09-15 | 1939-08-22 | Hanna Samuel Orr | Dust evacuating device |
US2187723A (en) * | 1938-07-27 | 1940-01-23 | Dow Chemical Co | Primary xenoxy-alkyl amines |
US2217660A (en) * | 1938-07-27 | 1940-10-15 | Dow Chemical Co | Secondary xenoxy-alkyl amines |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2879293A (en) * | 1957-02-19 | 1959-03-24 | Hoffmann La Roche | Benzylamine derivatives |
US3178420A (en) * | 1959-06-25 | 1965-04-13 | Richardson Merrell Inc | Amino-2-hydroxy-1-propoxy benzal derivatives of fluorene and xanthene |
US3213140A (en) * | 1960-09-06 | 1965-10-19 | Lilly Co Eli | 2-phenyl-4, 6-dichlorophenoxyethylamine and salts thereof |
US3139430A (en) * | 1960-12-20 | 1964-06-30 | Merck & Co Inc | 2-dialkylaminoalkoxy-6-substituted naphthalenes useful as new anticholesteremic agents |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2073677C1 (en) | Thienylcarboxylic acid and aminoalcohols esters, method of their synthesis and pharmaceutical composition showing anticholinergic activity | |
KR101221864B1 (en) | Hydrates and polymorphs of 4-[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)benzamide, methods for the production thereof, and use thereof as medicaments | |
JPS6056143B2 (en) | Amidine derivatives and their production method | |
PL179673B1 (en) | Method of obtaining novel esters of bi-and tricyclic amino-alcohols | |
NZ226089A (en) | Pyrimidinylamino derivatives of substituted piperidine; pharmaceutical compositions and processes of preparation | |
US2773900A (en) | Substituted aryl amino alkyl ethers | |
DK156722B (en) | ANALOGY PROCEDURE FOR PREPARING 2-PIPERAZINOPYRIMIDINE DERIVATIVES | |
EP0230020B1 (en) | 1,2,3,4,4a,9b-hexahydro-4a-aminoalkyldibenzofurans, a process for their preparation and their use as medicaments | |
Drake et al. | Some N1-(6-methoxy-8-quinolylaminoalkyl)-guanidines | |
CA1207774A (en) | 1-phenylindazol-3-one compounds, a method of preparing them and pharmaceutical compositions containing these compounds | |
US2906757A (en) | Their preparation | |
US3935196A (en) | Useful pro-drug forms of theophylline | |
US3213140A (en) | 2-phenyl-4, 6-dichlorophenoxyethylamine and salts thereof | |
US2786059A (en) | Derivatives of 2-nu-methyl-1, 2, 3, 4-tetrahydro-gamma-carbolines | |
US4002756A (en) | Useful pro-drug forms of theophylline | |
US3118941A (en) | N-(diethylaminoethyl)-n-propargylbenzylamines | |
KR880001715B1 (en) | Process for preparing 1-furyl-3,4-dihydro-isoquinolines | |
US2719846A (en) | 4[n-(beta-diethylaminoethyl) anilino]-pyrimidine and acid addition salts thereof | |
JPH0517443A (en) | Piperidine derivative | |
US3956391A (en) | Amino substituted tetrahydropleiadenes | |
JPS596851B2 (en) | piperidine derivatives | |
US4185104A (en) | Tranquillizing complexes | |
US2902491A (en) | N-(piperidyl-2-ethyl)-n-(mercaptophenyl)-anilines | |
US3635962A (en) | 4 - bis-morpholino- and 2 | |
US2715628A (en) | Thiophene derivatives |